A Study of Anti-PD-1 Combinations of D-CIK Immunotherapy and Axitinib in Advanced Ranal Carcinoma

NCT03736330 | Unknown Phase 2 DMC

• 1 other identifier: 2017-FXY-023-Urology
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and low dose anti-PD-1 antibody in patients with metastatic renal cell carcinoma treated with axitinib.

Conditions

Renal Cancer Metastatic

Keywords

Ranal Carcinoma; Immunotherapy; Axitinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate（ORR）by irRC and RECIST 1.1

  The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib,will be assessed using irRC and RECIST 1.1 to determine tumor response.

  3 years

Secondary Outcomes (5)

• Progression-free Survival（PFS）by irRC and RECIST 1.1

  3 years

• Overall Survival (OS) by irRC and RECIST 1.1

  3 years

• Duration of Response (DOR) by irRC and RECIST 1.1

  3 years

• The quality of life by EQ-5D-5L and NCCN-FACT FKSI-19 v2.0.

  3 years

• Severity of adverse events as assessed by CTCAE v4.0

  3 years

Study Arms (1)

Combinations treatment

EXPERIMENTAL

Drug: Axitinib 5mg orally twice a day Combination Treatment：Anti-PD-1 Combinations of D-CIK Immunotherapy

Biological: Combinations treatment

Interventions

Combinations treatment BIOLOGICAL

Autologous dendritic and cytokine-induced killer cells (D-CIK)(1.0-1.5\*10\^10 cells)were incubated with low dose anti-PD-1 antibody（pembrolizumab, Merck \& Co., Inc.） and were transferred to participants via intravenous infusion .

Also known as: pembrolizumab(Merck & Co., Inc.)

Combinations treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• advanced renal clear cell carcinoma confirmed by pathology: high-volume disease without systemic treatment(including primary lesion unable to surgery, multiple lymph node metastases or distant metastases), or achieved disease progression after treatment by the anti-angiogenesis therapy (TKI or mTOR inhibitors) or by cytokines or combination therapy
• Predicted survival \>=3 months
• At least 1 measurable lesion
• High-volume disease（meet one of the following criteria）:1. More than 3 sites of lesions with or without primary lesions, and at least 1 lesion routine CT or spiral CT scan \>=3cm; 2. Unresected primary lesions (\> 10cm), accompanied by 2 metastatic lesions; 3. After nephrectomy, single metastasis, at least 3 metastases, and at least one lesion \> 2cm; 4. After nephrectomy, multiple metastatic(\>3 organs) and at least one lesion \> 2cm.

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib
• Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components
• Severe cardiovascular and cerebrovascular diseases, uncontrollable severe hypertension and diabetes, severe renal insufficiency or uremia
• Long-term use of immunosuppressive agents after organ transplantation
• Immunosuppressive drugs are currently in use
• People with a clear and serious infection
• Predicted survival\<3 months
• Patients with T cell lymphoma, myeloma
• Patients with autoimmune diseases
• HIV positive, or other immunodeficiency diseases
• Pregnant or nursing

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (5)

• Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4.

  PMID: 22056247 RESULT

• Du Four S, Maenhout SK, De Pierre K, Renmans D, Niclou SP, Thielemans K, Neyns B, Aerts JL. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. Oncoimmunology. 2015 Jan 22;4(4):e998107. doi: 10.1080/2162402X.2014.998107. eCollection 2015 Apr.

  PMID: 26137411 RESULT

• Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015 Aug;14(8):561-84. doi: 10.1038/nrd4591.

  PMID: 26228759 RESULT

• Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.

  PMID: 25747273 RESULT

• Chen CL, Pan QZ, Weng DS, Xie CM, Zhao JJ, Chen MS, Peng RQ, Li DD, Wang Y, Tang Y, Wang QJ, Zhang ZL, Zhang XF, Jiang LJ, Zhou ZQ, Zhu Q, He J, Liu Y, Zhou FJ, Xia JC. Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with advanced solid tumors. Oncoimmunology. 2018 Jan 10;7(4):e1417721. doi: 10.1080/2162402X.2017.1417721. eCollection 2018.

  PMID: 29632736 RESULT

Study Officials

• Fangjian Zhou, MD.PhD

  Director of Urology,Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fangjian Zhou, MD.PhD

CONTACT

86-20-87343312; zhoufj@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Of Urology, Sun Yat-sen University Cancer Center

Model Details: Autologous D-CIK (1.0-1.5\*10\^10 cells) will be transferred to patients via intravenous infusion. Before cell transfer, D-CIK were incubated with anti-PD-1 antibody.

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 9, 2018
• Study Start: September 8, 2018
• Primary Completion: October 8, 2020
• Study Completion: November 8, 2021
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

CN (1)